The activation and selective transformation of virtually inexhaustible or easy-to-generate chemicals like N2, O2, CO2, CO, H2, or methane gas to value-added products is a lively area of current research, because of its economic relevance as well as its huge ecological impact. Biologists and chemists have put forth a lot of effort toward understanding and modeling the mechanisms of biological small-molecule activation, and in several catalytic cycles proposed for nickel-containing enzymes, nickel(I) plays a key role. In recent years also in synthetic chemistry the huge potential of complex nickel(I) units for the activation and transformation of small molecules has been discovered and exploited. This Perspective highlights some representative examples of nickel(I)-based small-molecule activation, intending to establish awareness of the competencies and scope of nickel(I) compounds.